Combating drug resistance by controlled release of BODIPY based nanoparticle and synergistic chemo-photodynamic effect

Abstract

Chemo-photodynamic therapy has received rapidly growing interests as one of the promising drug resistant cancer treatment. Herein, we developed a novel theranostic nanoscale drug delivery system (nDDS), which combines chemotherapy and photodynamic therapy (PDT) into modified single platform to achieve synergistic effects of these therapies on the treatment of drug resistant cancer cell. We synthesized chemo-photodynamic agents, amphiphilic benzyl poly (ethylene glycol)-diiodo substituted BODIPY conjugated with cisplatin (bPEG-DIBOC). The bPEG-DIBOC act as drug delivery system of photosensitizer and cisplatin. The cellular cisplatin uptake derived from the bPEG-DIBOC nanoparticles was much higher than that derived from cisplatin in A549 lung cancer cells and cisplatin-resistant A549/DDP lung cancer cells. The level of cellular reactive oxygen species (ROS) in the cell treated with bPEG-DIBOC was significantly elevated after light irradiation. Through these properties, the bPEG-DIBOC showed distinguished anticancer effects against A549/DDP cells with much lower concentration than free cisplatin. Consequently, this study proposes the outstanding potential of nDDS-based chemo-photodynamic therapeutic agent to circumvent drug resistance.